Long-term Stroke Recurrence in Atrial Fibrillation: Differential Predictors of Ischaemic and Haemorrhagic Risk

Background Predictors of long-term ischaemic and haemorrhagic stroke recurrence (LTSR) after acute ischaemic stroke (AIS) with AF remain uncertain. This study aimed to identify independent predictors of LTSR in patients with AF-related AIS. Methods We conducted a prospective observational study of consecutive AIS patients with AF enrolled in a hospital-based registry (January 2005–June 2022). The primary endpoint was LTSR, defined as any new ischaemic or haemorrhagic cerebrovascular event occurring during follow-up, which began 90 days after the AIS event. Independent predictors of overall, ischaemic, and haemorrhagic LTSR were identified using Fine–Gray competing risk models. Results A total of 1,212 patients (median age 79 years, 42.3% male) were included. During a median follow-up of 43.0 months, 220 patients (18.1%) experienced LTSR (incidence 0.039 events/person-year), predominantly ischaemic. In multivariable Fine–Gray models, known AF before the index stroke (sHR 2.1), large artery atherosclerosis (LAA) (sHR 2.6), small artery occlusion (SAO) (sHR 1.7), and higher CHA₂DS₂-VASc scores were independently associated with increased LTSR risk, while anticoagulation—particularly with Direct Oral Anticoagulants (DOACs) (sHR 0.46)—was protective. AF detected after stroke (AFDAS) (sHR 0.47) was associated with lower risk of ischaemic LTSR, and LAA defined a high-risk subgroup. Notably, SAO was the only independent predictor of haemorrhagic LTSR (sHR 3.2). DOAC showed a non-significant trend toward protection for haemorrhagic events. Conclusion In AF-related AIS, AFDAS was associated with lower risk of LTSR, while anticoagulation—particularly with DOACs—was strongly protective. The presence of competing stroke etiologies identified differential high-risk subgroups for ischaemic and haemorrhagic recurrence, highlighting the need for individualized prevention strategies.